Dopamine as additive to cold preservation solution improves postischemic integrity of the liver

Abstract

Dopamine pretreatment has been used to confer protection against cellular injury following hypothermia or anoxia, especially in vascular endothelial cells. Ischemia/reperfusion-associated tissue alterations still represent a major drawback in liver transplantation. The present study was aimed to investigate the effect of dopamine as an ex vivo adjunct, added to the cold storage solution, on cold preservation of the liver. Rat livers were excised 30 min after cardiac arrest, flushed with preservation solution and cold stored for 18 h. Dopamine (10, 50 or 100 microM) was added to the preservation solution in other livers. Organ viability was evaluated by 120 min of warm reperfusion in vitro (n = 6, resp.). Dopamine induced a dose related up to fourfold (at 50 mum) reduction in parenchymal (ALT, LDH) and mitochondrial (GLDH) enzyme release and significantly reduced histologic signs of tissue injury. Bile production and tissue ATP was doubled by dopamine. On the molecular level, dopamine enhanced postischemic phosphorylation of protein kinase A and p42/44 MAP kinase. Inhibition of cAMP-PKA pathway by simultaneous application of RP-cAMPs had no effect on P42/44 phosphorylation, or functional recovery of dopamine-treated grafts. Dopamine supplementation of the flush-out solution appears as a simple way for ex vivo augmentation of liver viability during preservation, not mediated via the catecholamine-cAMP signal cascade.